Advanced non-small cell lung cancer (NSCLC) has proven to be remarkably resistant to standard chemotherapy regimens. One potential alternative approach is the use of dose-intensive chemotherapy with supportive therapy such as granulocyte-colony stimulating factor (G-CSF). We conducted a randomized study of dose-intensive cisplatin/vindesine/mitomycin C chemotherapy (DI-PVM) and standard cisplatin/vindesine/mitomycin C chemotherapy (PVM). A total of one hundred patients with III-IV NSCLC was randomized. The DI-PVM consisted of 3 cycles of cisplatin: 80 mg/m2 (day 1), vindesine: 3 mg/m2 (days 1 and 8) and mitomycin C: 8 mg/m2 (day 1) in 3-week intervals with concurrent G-CSF. The PVM consisted of 2 cycles of the same chemotherapy in 4-week intervals. Blood cell counts were checked twice a week, and G-CSF (2 microgram/kg, SC) was administered when the count was </=2000/microliter. Eligibility criteria for this study were: no previous therapy, no active concomitant malignancy, ECOG PS </=1, age </=75 and adequate hematologic functions. The response rate for DI-PVM (26/50, 52%) was not significantly higher than that for PVM (22/50, 44%, chi2; p=0.423). However, progression-free survival for patients on DI-PVM was significantly longer than that of patients on PVM (23.7 versus 13.9 weeks, log-rank and generalized Wilcoxon test; p=0.006), as was overall median survival (57.0 versus 37.7 weeks, generalized Wilcoxon test; p=0.036). In addition, the difference in survival of patients with metastatic disease was significant (DI-PVM versus PVM; 48.9 weeks versus 23.9; p=0.032). Multivariate analysis showed that only ECOG PS was an independent prognostic variable in predicting response and survival on DI-PVM regimen. Hematological and non-hematological toxicities were equally frequent. The DI-PVM archived a longer survival than the PVM. The DI-PVM regimen should be considered a standard regimen for patients with metastatic NSCLC.